STAINES-UPON-THAMES, United Kingdom, June 13, 2019 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a global specialty biopharmaceutical company, is reporting that all primary and secondary outcome measures were met in its Phase 4, multicenter study assessing the efficacy and safety of Acthar® Gel (repository corticotropin injection, or RCI) in patients with persistently active RA who were previously treated with disease-modifying anti-rheumatic drugs (DMARDs) and corticosteroids. Encouraging topline data2 from the randomized, placebo-controlled, blinded, withdrawal phase of the study, as well as positive results from the open-label period of the study, were presented in a poster presentation on Thursday, June 13 at the European Congress of Rheumatology 2019 (EULAR) held June 12-15 in Madrid.

Acthar Gel is U.S. Food and Drug Administration (FDA)-approved as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in RA, including juvenile RA (selected cases may require low-dose maintenance therapy). Please see Important Safety Information for Acthar Gel below.

"This is the first reporting of the double-blind portion of the study, and the topline results showed that Acthar Gel has sustained effectiveness in patients with rheumatoid arthritis who were treated previously with multiple standard therapies but continued to have active disease," said Dr. Roy Fleischmann, Co-Medical Director of the Metroplex Clinical Research Center and Clinical Professor of Medicine at the University of Texas Southwestern Medical Center in Dallas. "We look forward to further reporting of the data in this important study."

Key Findings:

Randomized, Placebo-Controlled, Blinded, Withdrawal Period

A number of measures were assessed to evaluate sustained improvement:

Significantly more patients in the Acthar Gel group (62 percent) than in the placebo group (43 percent, P<0.05) had sustained LDA of <3.2 at Week 24, as assessed by the DAS28-ESR, a composite index that measures disease activity in patients with RA.

Significantly more patients in the Acthar Gel group (86 percent) than in the placebo group (66 percent, P≤0.05) had sustained low disease activity at Week 24, as defined by the Clinical Disease Activity Index (CDAI, Score ≤10), a composite measure of disease activity in patients with RA.

The primary endpoint of the study was the proportion of patients reaching LDA by DAS28-ESR of <3.2 at 12 weeks. The open-label analysis showed there was a decrease in the mean DAS28-ESR scores from baseline through Week 12, with 63 percent of patients who completed the open-label period achieving the LDA target at Week 12.

Acthar Gel was associated with significant improvements in DAS28-ESR and CDAI scores.

Significant improvements in additional efficacy measures were seen at Week 12, including fatigue, physical function, swollen joints and tender joints.

"We are pleased to report these positive results from the randomized, placebo-controlled, blinded, withdrawal phase of this important Acthar Gel study in underserved patients with such a debilitating disease," said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer at Mallinckrodt. "We are excited that our ongoing data generation efforts continue to confirm Acthar Gel is indeed an important therapeutic option for appropriate patients living with difficult-to-treat autoimmune disorders. We look forward to the continued emergence of data from other Acthar Gel ongoing studies across multiple disease areas."

Study Limitations

Sample bias may exist for the open-label phase of the ongoing study, and patients were aware that they were receiving Acthar Gel.4

Examiner bias may also exist as the patient had to reach low disease activity in order to enter the second phase of the study.4

The results cannot be solely attributed to Acthar Gel since patients were on different medications at the start of the trial and no washout periods were undertaken.4

About the StudyThe study was a Phase 4, multicenter, two-part study assessing the efficacy and safety of Acthar Gel in adult patients with RA with persistently active disease who were previously treated with corticosteroids and conventional synthetic and/or biologic DMARDs. The primary endpoint of the study was the proportion of patients reaching LDA at 12 weeks.

Part 1 of the study was an open-label period (n=259). After 12 weeks of treatment with Acthar Gel, patients were evaluated for treatment response using the DAS28-ESR. In Part 2 of the study (n=154), participants who achieved LDA of DAS28-ESR of <3.2 at Week 12 in Part 1 entered a double-blind withdrawal period, randomized in a 1:1 ratio to receive either Acthar Gel or matching placebo for an additional 12 weeks.

Full results from the randomized, placebo-controlled, blinded, withdrawal phase of the study are targeted for presentation at a research meeting later this year.

Find more information about the study here on the ClinicalTrials.gov website.

About Rheumatoid ArthritisRA is an autoimmune disease. It is a chronic condition that causes pain, stiffness, and swelling of the joints—all symptoms caused by inflammation.5 An estimated 1.5 million U.S. adults are living with RA.6 Treatment is aimed at stopping inflammation to put the disease in remission and relieve symptoms.7 Nonsteroidal anti-inflammatory drugs are used to ease symptoms whereas corticosteroids, disease-modifying anti-rheumatic drugs and biologics are used to slow down the disease activity.

Acthar Gel (repository corticotropin injection) IndicationsActhar Gel is an injectable drug approved by the FDA for the treatment of 19 indications. Of these, today the majority of Acthar use is in these indications:

Monotherapy for the treatment of infantile spasms in infants and children under 2 years of age

Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus

The treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown Acthar Gel to be effective in speeding the resolution of acute exacerbations of multiple sclerosis. However, there is no evidence that it affects the ultimate outcome or natural history of the disease

Inducing a diuresis or a remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus

Treatment during an exacerbation or as maintenance therapy in selected cases of systemic dermatomyositis (polymyositis)

The adverse effects of Acthar are related primarily to its steroidogenic effects

Acthar may increase susceptibility to new infection or reactivation of latent infections

Suppression of the hypothalamic-pituitary-axis (HPA) may occur following prolonged therapy with the potential for adrenal insufficiency after withdrawal of the medication. Adrenal insufficiency may be minimized by tapering of the dose when discontinuing treatment. During recovery of the adrenal gland patients should be protected from the stress (e.g. trauma or surgery) by the use of corticosteroids. Monitor patients for effects of HPA suppression after stopping treatment

Cushing's syndrome may occur during therapy but generally resolves after therapy is stopped. Monitor patients for signs and symptoms

Acthar can cause elevation of blood pressure, salt and water retention, and hypokalemia. Blood pressure, sodium and potassium levels may need to be monitored

Acthar often acts by masking symptoms of other diseases/disorders. Monitor patients carefully during and for a period following discontinuation of therapy

Acthar can cause GI bleeding and gastric ulcer. There is also an increased risk for perforation in patients with certain gastrointestinal disorders. Monitor for signs of bleeding

Acthar may be associated with central nervous system effects ranging from euphoria, insomnia, irritability, mood swings, personality changes, and severe depression, and psychosis. Existing conditions may be aggravated

Patients with comorbid disease may have that disease worsened. Caution should be used when prescribing Acthar in patients with diabetes and myasthenia gravis

Prolonged use of Acthar may produce cataracts, glaucoma and secondary ocular infections. Monitor for signs and symptoms

Acthar is immunogenic and prolonged administration of Acthar may increase the risk of hypersensitivity reactions. Neutralizing antibodies with chronic administration may lead to loss of endogenous ACTH activity

There is an enhanced effect in patients with hypothyroidism and in those with cirrhosis of the liver

Long-term use may have negative effects on growth and physical development in children. Monitor pediatric patients

Decrease in bone density may occur. Bone density should be monitored for patients on long-term therapy

Pregnancy Class C: Acthar has been shown to have an embryocidal effect and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus

Adverse Reactions

Common adverse reactions for Acthar are similar to those of corticosteroids and include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain

Specific adverse reactions reported in IS clinical trials in infants and children under 2 years of age included: infection, hypertension, irritability, Cushingoid symptoms, constipation, diarrhea, vomiting, pyrexia, weight gain, increased appetite, decreased appetite, nasal congestion, acne, rash, and cardiac hypertrophy. Convulsions were also reported, but these may actually be occurring because some IS patients progress to other forms of seizures and IS sometimes mask other seizures, which become visible once the clinical spasms from IS resolve

Other adverse events reported are included in the full Prescribing Information.

Mallinckrodt uses its website as a channel of distribution of important company information, such as press releases, investor presentations and other financial information. It also uses its website to expedite public access to time-critical information regarding the company in advance of or in lieu of distributing a press release or a filing with the U.S. Securities and Exchange Commission (SEC) disclosing the same information. Therefore, investors should look to the Investor Relations page of the website for important and time-critical information. Visitors to the website can also register to receive automatic e-mail and other notifications alerting them when new information is made available on the Investor Relations page of the website.

CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTSThis release includes forward-looking statements concerning Acthar Gel including expectations regarding its potential impact on patients and anticipated benefits associated with its use. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; issues with product quality, manufacturing or supply, or patient safety issues; and other risks identified and described in more detail in the "Risk Factors" section of Mallinckrodt's most recent Annual Report on Form 10-K and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law.